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Nat Commun. 2016 Dec 16;7:13696. doi: 10.1038/ncomms13696.

A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
2
Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.
3
Department of Immunology, Unit of Antibodies in Therapy and Pathology, INSERM U1222, Institut Pasteur, Paris 75015, France.
4
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA.
5
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Department of Medicine I, Research Laboratory of Infection Biology, Medical University of Vienna, Vienna 1090, Austria.
6
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
7
Institute for Immunology, Technische Universität Dresden, Dresden 01307, Germany.
8
Department of Microbiology and Immunology and Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California 94305, USA.

Abstract

Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG1 and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.

PMID:
27982078
PMCID:
PMC5171877
DOI:
10.1038/ncomms13696
[Indexed for MEDLINE]
Free PMC Article

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